Global, regional and national burden of trachea, bronchus, and lung cancer in middle-aged and elderly people aged 55+ years from 1990 to 2021, with projections to 2036: a systematic analysis of the Global Burden of Disease Study 2021

Introduction

While neoplastic diseases predominantly affect aging populations (1), global life expectancy has been substantially increased through advances in medical technologies and improved living standards. Notably, tracheal, bronchus, and lung (TBL) cancer, while maintaining peak incidence between the sixth and eighth decades of life (2), now demonstrate an expanding prevalence among middle-aged cohorts (3)—a demographic retaining significant productive life years. This epidemiological shift underscores the imperative for systematic evaluation of the evolving disease burden and epidemiological transitions within this critical age stratum.

TBL cancer remains major contributors to global cancer-related morbidity and mortality, though exhibiting marked geographical heterogeneity (4). Based on 2022 estimates from the International Agency for Research on Cancer Global Cancer Observatory, TBL cancer contributed to 2,480,301 new cases (12.4% of global cancer diagnoses) and 1,817,172 deaths (18.7% of all cancer-related mortality), ranking first in both incidence and mortality among all neoplasms (2). Population-based analyses from the US National Cancer Registry corroborate this pattern, demonstrating that 63.2% of cancer mortality reductions since 2010 have been driven by TBL cancer-specific interventions (3). However, global evidence remains fragmented. Most prior studies have emphasized mortality trends alone, neglecting multidimensional indicators such as disability-adjusted life-years (DALYs) and the Socio-Demographic Index (SDI). These indicators are essential to assess how economic growth, healthcare access, and social development jointly shape cancer outcomes and to identify persistent health inequities across countries and regions. Preliminary analyses have shown up to a 47.3-fold variation in age-standardized DALYs rates between high- and low-SDI regions (5), revealing a striking imbalance in the global distribution of disease burden and healthcare efficiency.

The Global Burden of Disease (GBD) serves as the only comprehensive framework for quantifying age-standardized incidence, mortality, and DALYs associated with neoplasms (6). Understanding these disparities holds major public health implications. Identifying regions where rapid socio-economic growth has not translated into proportional health gains is critical for optimizing cancer control strategies and resource allocation. A time-trend analysis based on GBD data can uncover whether improvements in cancer prevention and treatment have narrowed or widened existing inequities, and whether aging populations in lower-SDI regions face a disproportionate rise in burden. The predictive component of this study further enables policymakers to anticipate future healthcare demands and tailor interventions—such as early detection, tobacco control, and environmental exposure reduction—according to local demographic and economic contexts. However, no prior GBD analysis has specifically examined TBL cancer among adults aged ≥55 years—a population experiencing disproportionate longevity loss from malignancies. Therefore, this study aims to: (I) systematically assess temporal trends in TBL cancer burden from 1990 to 2021; (II) predict future mortality trends to 2036 across SDI and gender subgroups; and (III) quantify global, regional, and sex-specific disparities. The generated evidence will inform precision prevention strategies and guide equitable resource distribution to reduce global cancer inequalities. We present this article in accordance with the STROBOD reporting checklist (7) (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-693/rc).

Methods

Data source

The GBD database (https://ghdx.healthdata.org/gbd-2021) integrates data from multiple sources, including national cancer registries, vital registration systems, verbal autopsy reports, hospital discharge records, health surveys, and published epidemiological studies. To enable cross-population comparisons, age-standardized rates (ASRs) were computed using the GBD 2021 reference population, effectively controlling for demographic heterogeneity across regions. Incidence, mortality, and DALYs rates were extracted from the GBD 2021 analytical platform developed by the Institute for Health Metrics and Evaluation (IHME). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

The representativeness and reliability of GBD estimates vary by country depending on the completeness of national surveillance systems. For high-income and upper-middle-income regions with comprehensive cancer registries, data quality is generally robust. In contrast, for low- and middle-income regions with limited registry coverage, estimates rely more heavily on model-based imputations derived from covariates such as smoking prevalence, air pollution exposure, and healthcare access. To address potential underreporting, IHME applies a Bayesian meta-regression model (DisMod-MR 2.1) and a cause-of-death ensemble modeling framework (CODEm) to generate internally consistent estimates of incidence, mortality, and DALYs. Although these methods improve cross-country comparability, residual uncertainty remains, particularly in areas with sparse or incomplete data. Therefore, all reported estimates include 95% uncertainty intervals (UIs) to reflect statistical uncertainty and data limitations. All data undergo a multi-step quality control process and statistical harmonization to reduce inconsistencies across regions and years (8).

Statistical analysis

DALYs combine the impacts of both premature death and non-fatal health conditions, representing the total of years of life lost and years lived with disability (9). Temporal trends in incidence, mortality, and DALYs were investigated using join-point regression analysis (10). The Monte Carlo permutation test with 4,500 resampling’s—the default procedure in Joinpoint Software (v4.9.1.0)—was used to identify statistically significant trend inflection points, guided by Bayesian Information Criterion (BIC) minimization. Standard errors (SEs) for rate estimates were derived from GBD-reported confidence intervals (CIs), and the average annual percentage change (AAPC) was calculated through weighted summation of segment-specific slopes. The estimated annual percentage change (EAPC) was further derived by fitting linear regression models to the natural logarithm of ASR, providing a robust summary measure of temporal trends.

SE=UIupper−UIlower2×1.96[1]

where UI denotes uncertainty interval. AAPCs with 95% CIs were computed through weighted summation of segment-specific slopes:

AAPC={exp(∑wibi∑wi−1)}×100[2]

where b_i represents the slope coefficient for the i_th segment and w_i corresponds to time-interval weights (proportion of years spanned by each segment).

ln(ASR)=α+βx+ε[3]

where x denotes calendar year and ε represents the error term. The EAPC with 95% CIs was calculated as:

EAPC=100×(exp(β)−1)[4]

To evaluate healthcare system performance in relation to socio-demographic progress, a two-phase frontier analysis was conducted. Data envelopment analysis (DEA) using the ‘Benchmarking’ package in R (v4.3.1) established a production possibility frontier, identifying countries achieving maximal performance (efficiency score =1) and those with suboptimal performance (efficiency score <1). Stochastic frontier analysis (SFA) was subsequently applied to adjust for random error and quantify inefficiency gaps using the generalized health production function. Countries approaching the SDI-optimized frontier were considered efficiency leaders, while those with significant deviation were classified as lagging performers requiring policy attention (11).

Yit=f(Xit,β)+vit−uit[5]

Where:

Y_it: observed health outcome (DALYs) for country i in year t;

f(X_it,β): SDI-optimized theoretical minimum risk frontier;

v_it: exogenous stochastic noise;

u_it: healthcare system inefficiency;

Countries with u_it values approaching zero were classified as frontier-proximate achievers.

Results

Incidence, mortality, and DALYs of TBL among adults aged ≥55 years

According to GBD 2021 estimates, a total of 2,021,521 new cases of TBL cancer were reported worldwide among individuals aged 55 years and older. The global incidence of TBL cancer in this age group was associated with an ASR of 167.36 per 100,000 population. Regionally, East Asia exhibited the highest incidence, with 836,971 cases (ASR =271.83), followed by Western Europe, which recorded 273,869 cases (ASR =203.00). In contrast, regions in Sub-Saharan Africa, including Southern Sub-Saharan Africa (ASR =98.93) and Central Sub-Saharan Africa (ASR =50.18), reported substantially lower incidence rates. A notable gender disparity was observed, with men demonstrating a significantly higher global incidence ASR (243.99 per 100,000) compared to women (104.81 per 100,000), underscoring a pronounced sex-based difference in TBL cancer incidence.

Globally, TBL cancer accounted for 1,808,810 deaths among adults aged ≥55 years, with a mortality ASR of 152.44 per 100,000. The highest number of deaths was recorded in East Asia (742,883), followed by Western Europe (233,320) and Central Europe (74,575). Mortality rates were also highest in East Asia (ASR =249.25) and Western Europe (ASR =170.90), while regions in Sub-Saharan Africa exhibited lower mortality rates, with Eastern Sub-Saharan Africa (ASR =39.22) and Western Sub-Saharan Africa (ASR =27.12) reporting the lowest figures. Like incidence patterns, men experienced a significantly higher mortality ASR (225.79 per 100,000) compared to women (93.43 per 100,000), further emphasizing the sex-specific burden of TBL cancer.

In terms of DALYs, a total of 37,632,985 years were lost globally due to TBL cancer in individuals aged 55 years and older. East Asia contributed the highest burden, with 15,502,899 DALYs, followed by Western Europe (4,538,605) and Central Europe (1,637,723). The global average DALYs ASR stood at 2,892.52 per 100,000, with Western Europe reporting the highest rate (3,358.16 per 100,000), while the lowest was observed in Western Sub-Saharan Africa (536.87 per 100,000). Men exhibited a significantly higher DALYs ASR (4,246 per 100,000) compared to women (1,744.6 per 100,000), highlighting the disproportionate disease burden among male populations.

From a socio-demographic perspective, regions with high and high-middle SDI values exhibited the highest ASRs across incidence, mortality, and DALYs. High SDI regions recorded an incidence ASR of 226.08 per 100,000, a mortality ASR of 183.28 per 100,000, and a DALYs ASR of 3,460.56 per 100,000. Conversely, low SDI regions reported significantly lower ASR, with an incidence ASR of 31.31 per 100,000, a mortality ASR of 35.10 per 100,000, and a DALYs ASR of 706.23 per 100,000. A comprehensive summary of incidence, mortality, and DALYs estimates is provided in Table 1.

Patterns of change in incidence, mortality, and DALYs over time

The global trends in incidence, mortality, and DALYs of TBL cancer among individuals aged ≥55 years showed notable temporal changes from 1990 to 2021. The absolute number of new TBL cancer cases increased steadily over the study period, accompanied by a rise in the age-standardized incidence rate (ASIR). As shown in Figure 1A, the ASIR increased from approximately 100 per 100,000 in 1990 to over 200 per 100,000 in 2021, with higher rates consistently observed in males than in females. This increase was particularly pronounced in males, whose ASIR consistently exceeded that of females. Global TBL cancer mortality also showed an upward trend (Figure 1B). The number of deaths increased from around 1,000,000 in 1990 to more than 1,500,000 in 2021, while the age-standardized mortality rate (ASMR) exhibited a slight overall decrease. Similarly, the number of DALYs attributable to TBL cancer increased markedly (Figure 1C), rising from about 15 million in 1990 to over 25 million in 2021. In contrast, the age-standardized DALY rate (ASDR) showed a gradual downward trend throughout the same period.

Figure 1 Global trends in incidence, mortality, and DALYs of TBL cancer in individuals aged ≥55 years, 1990–2021, by sex. (A) Annual incidence number and age-standardized incidence rate per 100,000 population; (B) annual death number and age-standardized mortality rate per 100,000 population; (C) annual DALYs number and age-standardized DALYs rate per 100,000 population. DALYs, disability-adjusted life years; TBL, tracheal, bronchus, and lung.

Marked geographic heterogeneity ASIR of TBL cancer was observed worldwide. As shown in Figure 2A, the highest ASIRs were concentrated in high-income regions of Europe, North America, and Oceania, with particularly elevated values in Monaco, Denmark, the Netherlands, the United States, Canada, and Australia. In Asia, China, Japan, and the Republic of Korea also exhibited comparatively high incidence rates. Moderate ASIR levels were evident across parts of South America (notably Argentina and Chile) and Eastern Europe, as well as in several Central and East Asian countries. In contrast, most regions of Africa, particularly in Central and Western Africa, together with parts of South Asia, displayed the lowest incidence rates (<65 per 100,000). The map thus illustrates a distinct gradient from higher incidence in industrialized and higher-income countries to lower incidence in low- and middle-income regions, with the global extremes ranging from Monaco (446.85 per 100,000) to Nigeria (8.67 per 100,000).

Figure 2 Incidence analysis of TBL cancer among adults aged ≥55 years in 204 countries and territories. (A) Age-standardized rate (per 100,000) in 2021; (B) percentage change in TBL cancer cases from 1990 to 2021; (C) average annual percentage changes from 1990 to 2021; (D) estimated annual percentage changes from 1990 to 2021. AAPC, average annual percentage change; ASIR, age-standardized incidence rate; EAPC, estimated annual percentage change; NA, not available; TBL, tracheal, bronchus, and lung.

Further trend analysis using AAPC and EAPC revealed significant regional variations in the progression of TBL cancer burden. We assessed case changes in TBL incidence among individuals aged 55 years and older across 204 countries and territories from 1990 to 2021. The trends were categorized as decreasing (<0), increasing moderately [0–1), increasing substantially [1–2), and increasing dramatically (≥2), as illustrated in Figure 2B. AAPC analysis indicated that incidence rates declined in more than half of the countries worldwide, including Australia (AAPC, −0.56), Canada (AAPC, −0.81), the Democratic People’s Republic of Korea (AAPC, −0.10), and Denmark (AAPC, −0.46). Among them, 32 countries exhibited a significant decline (AAPC <−1), with the most pronounced reductions observed in Greenland (AAPC, −1.25), Kazakhstan (AAPC, −2.46), and Uzbekistan (AAPC, −2.47). In contrast, the remaining countries experienced varying degrees of increase, with Egypt (AAPC, 3.45) recording the highest growth globally. Detailed data are presented in Figure 2C and online table 1 (available at https://cdn.amegroups.cn/static/public/JTD-2025-693-1.xlsx).

EAPC analysis further highlighted substantial heterogeneity in incidence trends. Globally, EAPC values ranged from −4.35 (Kazakhstan) to +5.89 (Egypt). Significant declines (EAPC <−1.0) were observed in 18% of countries (38/204), whereas 12% (25/204) demonstrated substantial increases (EAPC >1.0). High-income regions, including Singapore [EAPC = −1.18 (95% CI: −2.03 to −0.31)], Australia [EAPC = −0.30 (95% CI: −1.01 to 0.42)], and the United States [EAPC = −1.33 (95% CI: −1.83 to −0.84)], exhibited sustained reductions. Conversely, sharp increases were noted in low- and middle-income regions, particularly in Egypt [EAPC = +4.82 (95% CI: 3.76 to 5.89)], Honduras [+2.08 (95% CI: 1.81 to 2.34)], and Lesotho [+2.58 (95% CI: 1.08 to 4.10)]. Comprehensive EAPC data are provided in Figure 2D and online table 2 (available at https://cdn.amegroups.cn/static/public/JTD-2025-693-2.xlsx).

Burden trends and predictions associated with the SDI

The relationship between SDI and the burden of TBL cancer, including mortality and DALYs, was analyzed across global regions and countries. The data revealed a distinct pattern in which regions with higher SDI, particularly high-SDI and high-middle SDI regions, exhibited a greater disease burden. Conversely, regions with low SDI demonstrated lower overall burden, although recent trends indicate an increasing trajectory in mortality and DALYs.

As illustrated in Figure 3A, the association between SDI and DALYs rates is not strictly linear. With increasing SDI, the ASDR for TBL cancer exhibits varying patterns across countries. For instance, lower-SDI countries, particularly in Africa and South Asia, generally display lower DALYs rates, whereas higher-SDI countries, including those in North America and Western Europe, tend to have significantly higher rates. Notably, the high-middle SDI region recorded the highest ASMR and ASDR in 2021, with values of 0.47 and 22.23 per 100,000 population, respectively (Table 1). This trend has evolved over time, with fluctuations in the TBL cancer burden observed across different SDI levels. While ASMR in low-SDI countries remained relatively stable from 1990 to 2021, high-SDI countries generally exhibited a declining trend over time.

Figure 3 Frontier analysis of TBL cancer ASDR and SDI over time [1990–2021] and in 2021. (A) Frontier analysis of TBL cancer ASDR and SDI from 1990 to 2021, with a color gradient representing years from dark blue [1990] to light green [2021]. The solid black line indicates the efficiency frontier. (B) Frontier analysis for 2021, where the solid black line defines the frontier, and individual countries and territories are represented as dots. The 15 countries with the largest effective difference are labeled in black. Countries with low SDI (<0.5) and low effective difference appear in blue, while those with high SDI (>0.85) and relatively high effective difference are shown in red. Green dots signify a decrease in TBL cancer ASDR, whereas orange dots indicate an increase from 1990 to 2021. ASDR, age-standardized disability-adjusted life years rate; DALYs, disability-adjusted life years; SDI, Socio-Demographic Index; TBL, tracheal, bronchus, and lung.

The 15 countries exhibiting the largest effective difference from the efficiency frontier (ranging from 190.77 to 8,032.69) were Turkey, Croatia, Bosnia and Herzegovina, Nauru, China, Greece, Denmark, Northern Mariana Islands, Serbia, Palau, Poland, Hungary, Montenegro, Monaco, and Greenland. These countries exhibited disproportionately high ASDR relative to their available sociodemographic resources. Conversely, countries on the efficiency frontier with low SDI and minimal effective difference included Niger, Somalia, Mali, Malawi, and Gambia. Countries with high SDI and relatively large effective differences included the USA, Belgium, Monaco, Denmark, and the Netherlands as depicted in Figure 3B. Comprehensive SFA data are provided in online table 3 (available at https://cdn.amegroups.cn/static/public/JTD-2025-693-3.xlsx).

Between 1990 and 2021, ASMR trends varied with SDI growth across different regions. Specifically, ASMR exhibited a positive correlation with SDI when SDI <0.75, peaking at SDI =0.75, after which a negative correlation was observed for SDI >0.75. Low-SDI regions, including Sub-Saharan Africa and parts of Southeast Asia, maintained relatively low ASMR with minimal fluctuations over time, showing neither significant increases nor decreases (Figure 4A). In contrast, Eastern Europe and parts of the Middle East (e.g., Russia, Ukraine, and Poland) consistently exhibited high lung cancer mortality rates (Figure 4A,4B), with little variation between 1990 and 2021. No substantial increases or declines were observed over this period. However, in high-income regions, lung cancer mortality rates demonstrated significant declines over time, reflecting notable health improvements. For example, Western Europe, North America, and parts of the Asia-Pacific region experienced a marked decrease in ASMR between 1990 and 2021 (Figure 4A).

Figure 4 Age-standardized mortality rates for TBL cancer among adults aged ≥55 years for regions (A) and countries (B) by SDI, from 1990 to 2021. ASMR, age-standardized mortality rate; SDI, Socio-Demographic Index; TBL, tracheal, bronchus, and lung.

Based on the autoregressive integrated moving average (ARIMA) model predictions, the TBL cancers ASMR is expected to follow distinct patterns across different SDI and gender groups from 2022 to 2036. In high SDI regions, continued decline in ASMR is projected for both males and females, albeit at a slower rate than before. In high-middle SDI regions, ASMR is expected to experience a relatively stable trend, with a more pronounced decline in males, while females are projected to exhibit an upward trend. In middle SDI, the ASMR is projected to stabilize after the previous fluctuations. In low-middle SDI, a continued increase in ASMR is forecasted, with a gradual increase for both genders. In low SDI, unlike other SDI groups, ASMR in this group exhibited fluctuations with an initial decline followed by an increase. Males are experiencing a slightly decline trend, while females exhibit a milder upward (Figure 5). These forecasts indicate that while higher SDI regions are expected to maintain their declining trend, lower SDI regions may continue to experience an increasing burden of lung cancer mortality.

Figure 5 Trends and projections of age-standardized mortality rates for TBL cancer among adults aged ≥55 years, by SDI regions and gender, from 1990 to 2036. ASMR, age-standardized mortality rate; SDI, Socio-Demographic Index; TBL, tracheal, bronchus, and lung.

Discussion

A comprehensive analysis and predictions of TBL cancer burden among middle-aged and elderly ≥55 years across 204 countries from 1990 to 2021 reveals profound disparities in incidence, mortality, and DALYs, shaped by a complex interplay of aging populations, environmental carcinogens, socioeconomic transitions, and healthcare inequities. While our findings align with global cancer surveillance trends (12,13), three critical dimensions warrant further investigation: (I) the paradoxical role of socioeconomic development in modulating risk factors; (II) the unresolved gender disparity in mortality despite narrowing incidence gaps; and (III) the urgent need for precision prevention strategies targeting region-specific etiological drivers.

Socioeconomic development: a double-edged sword in TBL epidemiology

The stark contrast in ASIR between high-SDI (226.08 per 100,000) and low-SDI regions (31.31 per 100,000) underscores the dual impact of industrialization. In high-income nations, prolonged tobacco use—a legacy of the 20th-century smoking epidemic—remains the dominant driver (14,15). For instance, Central Europe’s ASIR of 222.08 reflects persistent smoking prevalence among males (356.05 per 100,000), consistent with historical cohort studies attributing 85% of TBL cancer deaths to smoking (14,16). Notably, the observed continuous decline in TBL cancer mortality in high-SDI regions aligns with well-established public health interventions and advancements in medical treatment (17). Countries with high SDI scores, such as the United States and Western European nations, have implemented aggressive tobacco control policies, including high taxation, smoking bans, and anti-smoking campaigns, which have led to substantial reductions in smoking prevalence (18). However, despite these successes in high-SDI regions, the high-middle SDI regions present a more complex picture. These regions exhibit the highest ASMR for TBL cancer, with a value of 204.76 per 100,000 (Table 1). This paradox is rooted in several interrelated factors. While these countries have experienced significant socioeconomic development, public health infrastructure and cancer control measures have not fully caught up with their economic progress (19). In some cases, the health burden of aging populations, particularly those with prolonged smoking histories, exceeds the capacity of healthcare systems to provide timely diagnosis and treatment. One potential explanation for the high mortality rate in middle-income countries is the “transition period” where the benefits of tobacco control policies have not yet outweighed the historical burden of smoking. While tobacco use has decreased in younger generations due to public health measures, older cohorts continue to experience higher rates of TBL cancer mortality due to accumulated exposure to smoking and environmental carcinogens. Additionally, many high-middle SDI countries have not yet implemented the same level of aggressive cancer screening and early detection programs that are seen in high-SDI regions (20).

In middle- and low-middle SDI regions, the interaction between demographic aging and environmental risk exposures may synergistically amplify the TBL cancer burden. Older adults are biologically more vulnerable to inhaled carcinogens due to cumulative lifetime exposure, impaired DNA repair mechanisms, and reduced cardiopulmonary reserve (1,21). When combined with sustained smoking prevalence and worsening air-quality indicators, this results in a “double-hit” effect on lung tissue integrity. Epidemiologic modeling from China and Eastern Europe suggests that each 10 µg/m³ increase in long-term particulate matter 2.5 (PM2.5) exposure can elevate lung cancer mortality by 8–12%, and that the relative risk is significantly higher in ever-smokers than in never-smokers (22-24). The coexistence of aging populations and persistent exposure to PM2.5 and tobacco smoke in many middle-income countries—where industrial emissions and biomass combustion remain prevalent—therefore acts as a major driver of the plateauing or even rising age-standardized mortality observed in our analysis. Furthermore, research have identified an additive or multiplicative relationship between tobacco use and air pollution. A large prospective cohort study of nearly 1.2 million participants have shown that there is a small increase in lung cancer risk when individuals are exposed to both cigarette smoking and fine particulate matter, beyond what would be expected from the sum of individual exposures (25). This combined exposure burden may explain why high-middle-SDI regions—despite socioeconomic advancement—continue to exhibit elevated DALYs. Rapid urbanization and motorization have intensified fine-particulate pollution, while tobacco control enforcement often lags industrial growth. As a result, these societies face the paradox of “development-related exposure accumulation”, in which progress in life expectancy inadvertently enlarges the population at risk.

Conversely, in low-SDI regions, TBL cancers mortality exhibits a fluctuating pattern, with an overall upward trend projected for the coming decades. Many low-income countries have been slow to adopt stringent anti-smoking measures, leading to persistently high smoking rates, particularly among men (12). Besides, unregulated indoor air pollution [e.g., biomass fuel use in South Asia (26)] and occupational hazards [e.g., asbestos exposure in Sub-Saharan Africa (27)] may make the trend even more pessimistic. However, this progress is counterbalanced by aging demographics, which amplify absolute case numbers (13,28). The nonlinear relationship between SDI and DALYs further highlights structural inequities. While high-SDI nations benefit from early detection [e.g., low-dose computed tomography screening reducing mortality by 20% (29)], low-resource settings face diagnostic delays and fragmented palliative care (30,31). This divergence is exemplified by East Asia’s disproportionate DALYs burden (4,630.15 per 100,000), where rapid urbanization exacerbates PM2.5 exposure (21,22,32) while healthcare access remains stratified (31).

Gender disparities: beyond smoking prevalence

Globally, male TBL cancer mortality remains significantly higher than in females, with male mortality rates (225.79 per 100,000) being approximately three times that of females (93.43 per 100,000). This disparity has traditionally been attributed to higher smoking prevalence among men, who have been the primary target of tobacco consumption in many regions (14,15). However, this gender gap is not entirely explained by smoking alone, and emerging evidence points to other factors that contribute to the widening or narrowing of this disparity, especially as smoking patterns evolve.

Our analysis reveals a narrowing of the male-to-female ASIR, from 3.1 in 1990 to 2.33 in 2021, suggesting that novel risk factors are emerging among women. Particulate matter (PM2.5) and household air pollution are significantly linked to lung cancer risk in females, particularly in Southeast Asia. Multiple studies provide strong evidence of this connection (21,33). Besides, hormonal influences are believed to be a critical factor in the gender disparity observed in lung cancer. Recent studies have suggested that exposure to certain environmental carcinogens, may interact with genetic and hormonal pathways (34,35), such as estrogen receptor signaling (36), which can promote the development of adenocarcinoma subtypes (27), a cancer type that is more prevalent in women than in men. In Taiwan, a positive association was found between long-term residential exposure to PM2.5 at levels above 30 µg/m³ and the incidence of lung adenocarcinoma (37), suggesting that women may be more susceptible to developing lung cancer even in the absence of heavy smoking.

Furthermore, gender-specific barriers significantly impede lung cancer diagnosis and care for women, with systemic biases and societal stigma contributing to delayed detection and poorer outcomes. Multiple studies highlight these disparities. Rana et al. found that women consistently experience longer diagnostic intervals, with substantial heterogeneity in treatment access (38). Similarly, Agbedinu et al. revealed that in low- and middle-income countries, women face various barriers, including financial challenges (65.5%), geographical obstacles (34.5%), and health system limitations (55.2%), leading to an average delay of 7.4 months from symptom onset to diagnosis (39). Further confirming these disparities, Kearney et al. noted that women, along with other marginalized groups, experience significant gaps throughout the lung cancer care continuum (40). Societal stigma and healthcare system biases exacerbate these challenges, ultimately compromising women’s cancer outcomes (41).

Addressing these disparities requires the integration of gender-specific risk mitigation strategies into public health interventions. Gender-tailored prevention and screening programs are crucial, particularly for high-risk women who may not benefit from general smoking cessation campaigns. Current tobacco control policies, which have predominantly targeted male smokers, have failed to adequately address the needs of female smokers, leaving women more vulnerable as smoking prevalence rises among them (42,43). There is an urgent need for tobacco cessation programs that consider the unique social, cultural, and psychological factors influencing smoking behavior in women to help close the gender gap in lung cancer mortality. Policies that specifically target the environmental and biological risk factors contributing to lung cancer in women will be essential for reducing the global gender disparity in tobacco-related lung cancer outcomes.

Toward precision prevention: molecular insights and policy integration

The heterogeneity of EAPC across countries (ranging from −3.2% to +2.1%) highlights the inadequacy of one-size-fits-all interventions. In high-incidence regions (e.g., East Asia), integrating genomic screening for epidermal growth factor receptor (EGFR) mutations—prevalent in non-smoking lung cancer patients (27,36)—could enhance early detection and treatment outcomes (44). For example, EGFR mutations are found in a substantial proportion of lung adenocarcinomas in East Asia, where non-smoking-related lung cancer is more common than in other regions. Studies have shown that targeted therapies, such as tyrosine kinase inhibitors (TKIs), can greatly improve survival rates in patients with EGFR mutations, resulting in better long-term outcomes and quality of life (44). However, the impact of EGFR testing on reducing DALYs in these high-burden regions must be considered within the broader context of healthcare infrastructure and access to treatment. While genomic screening has proven to be effective in reducing cancer burden in high-SDI countries, its application in low- and middle-income regions presents a different set of challenges. The cost-effectiveness of implementing EGFR mutation testing in resource-limited settings, where healthcare resources are constrained and access to advanced therapies may be limited, remains a critical question. Several studies have explored the cost-effectiveness of genomic screening in such regions, suggesting that while the initial cost of testing can be high, the long-term benefits in terms of survival improvement and reduced healthcare expenditures may justify the investment, especially when paired with early treatment initiation (45,46). Meanwhile, low-SDI regions require cost-effective strategies to mitigate combustion-related carcinogens. Notably, randomized trials in rural India have demonstrated that the adoption of clean cookstoves reduces polycyclic aromatic hydrocarbon exposure by 50% (26,32), underscoring the potential of targeted environmental interventions.

Our frontier analysis (Figure 3) identifies that some countries (e.g., Chile, Turkey) experience development progress that does not proportionally translate to improved health outcomes, creating a misalignment between socio-demographic gains and disease burden reduction. Karahasan et al. [2017] specifically highlighted Turkey’s “spatial dichotomy” in health indicators, indicating that development does not uniformly improve health outcomes (47). Ghadimi et al. [2018] further supports this by showing that country-level health-related sustainable development goals (SDG) index values varied substantially, even within countries, suggesting complex dynamics between development progress and health improvements (48). While the specific details of the referenced Figure 3 are not available, the sources collectively validate the concept of potential misalignment between SDI gains and DALYs reductions.

Limitation

This study is subject to several important limitations. First, our analysis is based on the GBD 2021 estimates of incidence, mortality and DALYs. Although the GBD study provides one of the most comprehensive global health databases, its estimates are inherently constrained by its reliance on national surveillance systems of widely varying completeness and quality. This variability is a well-recognized challenge. Recent studies have consistently shown that the performance of these systems differs significantly across countries (49), with large gaps in system construction, management, and data reporting quality for major diseases (50). The situation is often most acute in low-resource settings where the disease burden is highest, yet surveillance systems are the weakest and can be affected by design biases (51). Furthermore, a multi-country survey revealed that surveillance data is often fragmented, facing common barriers related to data integration, information technology, and financial resources (52). Consequently, while the GBD provides invaluable insights, the limitations of its underlying data sources must be considered when interpreting its findings. Furthermore, the study is limited by the lack of granular data on specific risk factors, such as detailed tobacco product usage and differentiated sources of PM2.5, including biomass and industrial pollution. This data gap hinders the ability to perform more targeted etiological analyses, which could provide deeper insights into the differential impact of various risk exposures on lung cancer incidence. Addressing this limitation in future research would allow for a more refined understanding of the specific contributions of different environmental and behavioral factors to cancer burden.

Second, efficiency frontier analysis via DEA/SFA oversimplifies healthcare system performance by relying heavily on socio-demographic indices, potentially masking critical systemic factors that influence real-world health outcomes. As earlier studies applying similar methodologies have acknowledged, this approach can overlook the influence of institutional and environmental characteristics (53). Frontier analysis techniques often fail to adequately capture complex contextual factors such as health-workforce density, facility readiness, regulatory landscapes, and local infrastructure (54). Consequently, the estimated ‘efficiency gaps’ in our study may conflate true managerial inefficiency with unobserved systemic heterogeneity, a known methodological challenge in frontier analysis, highlighting the need for more nuanced, context-sensitive performance evaluation methodologies. Therefore, our findings on ‘efficiency gaps’ should be interpreted as indicative rather than causal, serving to highlight areas for further investigation rather than to assign definitive causes.

Third, from a methodological viewpoint, our forecasting approach using the ARIMA model captures historic trends but does not account for potential disruptive changes such as accelerated implementation of tobacco control policies, large-scale air-quality improvements or the introduction of novel therapies (e.g., immune checkpoint inhibitors in lung cancer) which could markedly alter future trajectories. Such “policy or technological shock” effects are not built into ARIMA outcomes and thus our projections to 2036 should be interpreted as baseline scenarios under status-quo conditions rather than as definitive forecasts sensitive to intervention (55,56). Another limitation of this study is its focus on adults aged 55+ years, excluding younger populations who may be experiencing shifts in TBL incidence due to emerging risk factors, such as adolescent e-cigarette use. As vaping becomes increasingly prevalent, particularly among younger cohorts, it could significantly alter the future trajectory of lung cancer incidence. Future research should incorporate these younger populations to capture the full impact of new risk behaviors and their potential long-term effects on TBL cancer burden.

Despite these limitations, we believe they do not undermine the core findings of our analysis: the relative ordering of burdens by SDI strata, sexes and regions remained consistent across multiple metrics (incidence, mortality, DALYs) and over long timespans. To enhance precision and policy relevance, future research should aim to strengthen cancer registry coverage and exposure assessment in resource-limited settings while integrating higher-resolution data on tobacco types and pollutant sources. Moreover, it should prioritize the development of predictive models that incorporate policy interventions and treatment scenarios rather than relying solely on trend-based extrapolations. Expanding efficiency analyses to include explicit indicators of health-system capacity—such as screening uptake, workforce availability, and infrastructure quality—would further refine burden estimates and increase their practical value in guiding global cancer-control strategies.

Conclusions

This study provides a comprehensive assessment and predictions of the global, regional, and national burden of trachea, bronchus, and lung cancer among middle-aged and elderly populations (aged ≥55 years) from 1990 to 2021. Our findings reveal significant geographic and temporal variations in TBL cancer incidence, mortality, and DALYs, highlighting both progress and persistent disparities in disease burden.

Despite advancements in early detection, treatment, and tobacco control policies, TBL cancer continues to be a major contributor to both morbidity and mortality worldwide, particularly in high-income and rapidly developing regions. The observed declines in TBL cancer burden in certain high-income countries underscore the effectiveness of sustained public health interventions, while the increasing burden in low- and middle-income regions suggests the urgent need for targeted policies addressing tobacco consumption, air pollution, and occupational exposures.

Gender and age-specific trends indicate that men continue to bear a disproportionately higher TBL cancer burden, though incidence and mortality rates among women are rising in several regions, likely reflecting evolving smoking patterns and environmental risk factors. Additionally, the growing contribution of aging populations to the overall TBL cancer burden underscores the necessity of age-specific prevention and management strategies.

Moving forward, global efforts should prioritize comprehensive tobacco control measures, improved access to early diagnosis and treatment, and targeted interventions for high-risk populations. Strengthening healthcare infrastructure, enhancing surveillance systems, and addressing socioeconomic determinants of health will be critical in reducing TBL cancer-related disparities and improving outcomes worldwide.

While progress has been made, TBL cancer remains a major public health challenge, necessitating sustained and region-specific interventions to mitigate its burden. Future research should focus on evaluating the impact of emerging risk factors, optimizing screening strategies, and advancing precision medicine approaches to enhance disease prevention and treatment global.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBOD reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-693/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-693/prf

Funding: This work was supported by Beijing Hope Run Special Fund of Cancer Foundation of China (No. LC2018L01), CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2023-I2M-C&T-B-100), Beijing Natural Science Foundation (No. L246013), and Bethune Ethicon Excellent Surgery Foundation (No. CESS2021TB02).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-693/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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